Introduction to Evidence-Based Medicine

1. Introduction to Evidence-Based Medicine Gregory W. Dalack, MD December 22, 2005

2. What is EBM? • The integration of: • Best Research Evidence with • Clinical Expertise and • Patient Values • Sackett et al., 2000

3. Research Evidence: clinically relevant research, sometimes from basic sciences, often from clinical research studies examining diagnostic tests, markers of prognosis, safety and efficacy of treatment rehabilitative or preventive regimens

4. Clinical Expertise: using our clinical skills and past experience to identify health states, diagnosis, risks and benefits for individual patients, and integrate their …

5. Patient Values: the unique concerns, expectations and preferences each patient brings to that particular clinical encounter. We incorporate these into clinical-decision making as part of our collaborative treatment with the patient.

6. EBM arising from Challenges and Opportunities • Daily need for valid information in clinical settings (diagnoses, prognoses, treatment and prevention information) • Inadequacy of traditional information sources (textbooks, experts, voluminous and variable quality publications) • We note an increase in our diagnostic skills and clinical judgment with time and experience, but a decline in up-to-date knowledge • Lack of time for in-depth search and evaluation of information pertinent to our clinical work

7. JASPA*(Journal associated score of personal angst) J: Are you ambivalent about renewing your JOURNALsubscriptions? A: Do you feel ANGER towards prolific authors? S: Do you ever use journals to help you SLEEP? P: Are you surrounded by PILESof PERIODICALS? A: Do you feel ANXIOUS when journals arrive? 0 (?liar) 1-3 (normal range) >3 (sick; at risk for polythenia gravis and related conditions) * Modified from: BMJ 1995;311:1666-1668

8. EBM arising from Challenges and Opportunities • Development of strategies to efficiently track down and appraise evidence, evaluate its validity and relevance • Development of systematic reviews and concise summaries (e.g., Cochrane Reviews) • Creation of Evidence-based Journals of secondary publication (pull together the small fraction of articles that are both valid and of immediate clinical use) • Information systems at our fingertips • Development of strategies for life-long learning to improve clinical performance

9. The Practice of EBM • Step 1: Asking an answerable question • Step 2: Tracking down the best evidence to answer that question • Step 3: Critically appraise the evidence for validity, size of the effect, and utility of the findings • Step 4: Incorporate the clinical appraisal into our clinical expertise and patient’s individual issues • Step 5: Evaluate and improve steps 1-4 with each new opportunity to apply these principles

10. Limitations • Shortage of coherent, consistent, valid and information • Difficulties in applying evidence to the care of individual patients • Other barriers to the practice of high quality medicine

11. EBM does not • Deny the importance of clinical experience • Ignore patient values and preferences • Promote a “cookbook” approach to medicine or health care

12. Good clinical questions • “Background” Questions • General knowledge • Two components • Root (who, what, when, where, why) • A disorder or aspect of a disorder • E.g., “What is the typical age of onset of bipolar disorder?” • “How do I decide to use a typical vs. atypical antipsychotic for agitation?”

13. Good clinical questions • “Foreground” Questions • These ask for specific information about managing a patient with a disorder • They have 3-4 essential components

14. Asking answerable clinical questions (CEBM- Oxford)

15. 56 year old African-American veteran is noted to be delirious and agitated post-operatively after hernia repair. • He has no hx of alcohol abuse/dependence and is otherwise healthy • Your attending recommends using haloperidol to manage the agitation; a visiting consultant recommends lorazepam

16. Asking answerable clinical questions (CEBM- Oxford)

17. Forming the Clinical Question • In a 56 year old man with post-op delirium and agitation, • does treatment with haloperidol vs. lorazepam • result in greater improvement in agitation?

18. Finding the Best Evidence • Typically not in textbooks (quickly obsolete) • Difficult with traditional journals • Use electronic databases, some which explicitly evaluate the evidence • Evidence-based Medicine Reviews (EBMR) • Cochrane Database of Systematic Reviews

19. UM Medsearch • EBM Reviews- available on Ovid • Cochrane Database of Systematic Review  • ACP Journal Club  • Database of Abstracts of Reviews of Effects • Cochrane Central Register of Controlled Trial • “haloperidol and lorazepam”- 106 references • Combine with “delirium”- 11 references

20. Drug therapy for delirium in terminally ill patients • Jackson, KC; Lipman, AG • Date of Most Recent Update: 21-October-2004 • Date of Most Recent Substantive Update: 18-February-2004 • Cochrane Pain, Palliative and Supportive Care Group. • Dr. Kenneth Jackson, II, PharmD, Clincal Pharmacist, Pain/Palliative Care

21. AbstractBackground: Delirium is a common disorder that often complicates treatment in patients with life-limiting disease. Delirium is described using a variety of terms such as agitation, acute confusional states, encephalopathy, organic mental disorders, and terminal restlessness. Delirium may arise from any number of causes, and treatment should be directed at addressing these causes. In cases where this is not possible, or does not prove successful, the use of drug therapy may become necessary. • Objectives: The primary objective of this review was to identify and evaluate studies examining medications used to treat patients suffering from delirium during the terminal phases of disease. • Search strategy: We searched the following sources: MEDLINE (1966 to July 2003), EMBASE 1980 to July 2003), CINAHL (1982 to July 2003), PSYCH LIT (1974 to July 2003), PSYCHINFO (1990 to July 2003) and the Cochrane Library Volume 2, 2003) for literature pertaining to this topic.

22. Selection criteria: Prospective trials with or without randomization and/or blinding involving the use of pharmacological agents for the treatment of delirium at the end of life were considered. • Data collection and analysis: Two reviewers independently assessed trial quality using standardized methods and extracted data for evaluation. Outcomes related to both efficacy and adverse effects were collected.

23. Main results: Thirteen potential studies were identified by the search strategy. Of these, only one study met the criteria for inclusion in this review. This study evaluated 30 hospitalized AIDS patients receiving one of three different agents: chlorpromazine, haloperidol, and lorazepam. Analysis of this trial found chlorpromazine and haloperidol to be equally effective. Chlorpromazine was noted to slightly worsen cognitive function over time but this result was not significant. The lorazepam arm of the study was stopped early as a consequence of excessive sedation. • Conclusions: The data from one study of 30 patients would perhaps suggest that haloperidol is the most suitable drug therapy for the treatment of patients with delirium near the end of life. Chlorpromazine may be an acceptable alternative if a small risk of slight cognitive impairment is not a concern. However, there is insufficient evidence to draw any conclusions about the role of pharmacotherapy in terminally ill patients with delirium, and further research is essential.

24. Delirium: prevention, treatment, and outcome studies (Structured abstract) • [Not stated] • Centre for Reviews and Dissemination • Date of Most Recent Update: 2000 • NHS Centre for Reviews and Dissemination. University of York, York, U.K. • Abstract and Commentary for:Cole M G, Primeau F J, Elie L M, Delirium: prevention, treatment, and outcome studies. Journal of Geriatric Psychiatry and Neurology, 1998;11(3):126-137.

25. Results of the review • Treatment studies (13 studies overall; 6 pharmacotherapy, 7 non- pharmacotherapy): • Non-pharmacotherapy interventions appeared to have a beneficial effect… • For pharmacotherapy, results from one RCT suggested that haloperidol and chlorpromazine were more useful than lorazepam in improving delirium in younger AIDS patients, one cohort study reported that haloperidol was more useful than narcotics in controlling delirium in older cardiac patients, and two non-randomised trials reported that mianserin was as effective as haloperidol in controlling symptoms in older medical-surgical and psychiatric patients. • For both prevention and treatment studies, there were frequent flaws in study design, including non-randomised designs, differences between treatment and control groups at baseline, and outcomes not rated blind. • Findings from a third literature review of outcome (prognostic) studies suggested that better premorbid function (i.e. admission from home or to a surgical unit) was the most important predictor of better outcomes.

26. 28 year old Caucasian woman presents with first episode of Major Depression. She has also recently become pregnant and is worried about the effect of medication on her pregnancy • You need to treat and must consider treatment options

27. Asking answerable clinical questions (CEBM- Oxford)

28. Forming the Clinical Question • In a 28 year old pregnant woman with Major Depression • Would psychotherapy treatment vs. a trial of antidepressant medication • be effective?

29. Same databases to search • “psychotherapy and antidepressant medication” 176 hits • Combine with “Major Depression” (2207) yields 62 hits • Hit #41: Review: Cognitive therapy is beneficial and equivalent to behaviour therapy and antidepressants for mild-to-moderate depression

30. Main results: 78 trials were identified of which 48, including 2765 patients, met the selection criteria. In the 20 studies that compared CT with waiting list or placebo, the average patient in the CT group was 29% better than the average patient in the control group after treatment (effect size 0.82, P < 0.001). In the 17 trials that compared CT with antidepressants, the average patient in the CT group was 15% better than the average patient in the antidepressant group after treatment (effect size 0.38, P < 0.001). In the 22 trials that compared CT with a group of miscellaneous therapies (including psychodynamic, interpersonal, non-directive, supportive, and relaxation therapies, and alternative bibliotherapy), the average patient in the CT group was 10% better than the average patient in any of the other groups after treatment (effect size 0.24, P < 0.01)… • Conclusion: In patients with mild-to-moderate depression, cognitive therapy has a beneficial effect equivalent to that of behaviour therapy and that of antidepressants and a group of other miscellaneous therapies.

31. EBM • Ask an answerable question • Track down the evidence • Critically appraise the evidence • Integrate the appraisal with clinical expertise and patient’s needs and values • Evaluate steps 1-4 and improve ability to execute them efficiently and effectively

32. EBM • Upcoming topics: • Searching the literature • Appraising the evidence on your own • EBM and biostatistics • Plan to incorporate EBM training into the curriculum • Make it (almost) a daily clinical activity